title: Levofloxacin rescues mice from lethal intra-nasal infections with virulent Francisella tularensis and induces immunity and production of protective antibody.
abstract: The ability to protect mice against respiratory infections with virulent Francisella tularensis has been problematic and the role of antibody-versus-cell-mediated immunity controversial. In this study, we tested the hypothesis that protective immunity can develop in mice that were given antibiotic therapy following infection via the respiratory tract with F. tularensis SCHU S4. We show that mice infected with a lethal dose of SCHU S4, via an intra-nasal challenge, could be protected with levofloxacin treatment. This protection was evident even when levofloxacin treatment was delayed 72h post-infection. At early time points after levofloxacin treatment, significant numbers of bacteria could be recovered from the lungs and spleens of mice, which was followed by a dramatic disappearance of bacteria from these tissues. Mice successfully treated with levofloxacin were later shown to be almost completely resistant to re-challenge with SCHU S4 by the intra-nasal route. Serum antibody appeared to play an important role in this immunity. Normal mice, when given sera from animals protected by levofloxacin treatment, were solidly protected from a lethal intra-nasal challenge with SCHU S4. The protective antiserum contained high titers of SCHU S4-specific IgG2a, indicating that a strong Th1 response was induced following levofloxacin treatment. Thus, this study describes a potentially valuable animal model for furthering our understanding of respiratory tularemia and provides suggestive evidence that antibody can protect against respiratory infections with virulent F. tularensis.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA. gklimpel@utmb.edu
authors.forename: Gary R
authors.initials: GR
authors.lastname: Klimpel
authors.forename: Tonyia
authors.initials: T
authors.lastname: Eaves-Pyles
authors.forename: Scott T
authors.initials: ST
authors.lastname: Moen
authors.forename: Joanna
authors.initials: J
authors.lastname: Taormina
authors.forename: Johnny W
authors.initials: JW
authors.lastname: Peterson
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Chopra
authors.forename: David W
authors.initials: DW
authors.lastname: Niesel
authors.forename: Paige
authors.initials: P
authors.lastname: Carness
authors.forename: Judith L
authors.initials: JL
authors.lastname: Haithcoat
authors.forename: Michelle
authors.initials: M
authors.lastname: Kirtley
authors.forename: Abdelhakim Ben
authors.initials: AB
authors.lastname: Nasr
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000907:Antibodies, Bacterial / Q000032:analysis / Q000096:biosynthesis*; D000917:Antibody Formation / Q000276:immunology; D015169:Colony Count, Microbial; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005604:Francisella tularensis / Q000472:pathogenicity; D064704:Levofloxacin; D051379:Mice; D008807:Mice, Inbred BALB C; D015242:Ofloxacin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016019:Survival Analysis; D014406:Tularemia / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D014774:Virulence; D015047:Zoonoses / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D064704:Levofloxacin; D015242:Ofloxacin